Nanotechnology has made remarkable contributions to clinical oncology. Nanotherapeutics and diagnostic tools have distinctive characteristics which allow them superior abilities to deliver therapeutics and imaging agents for radiation oncology. Compared to solid biopsies and imaging, the analysis of circulating tumor cells (CTCs) offers a more rapid, real-time, and less invasive method to monitor the dynamic molecular profiles of tumors. The potential of CTCs to be translated as a novel cancer biomarker has been demonstrated in numerous clinical studies. This review will discuss clinical applications of nanomaterials in radiation oncology and the implication of CTCs in cancer detection and monitoring.